Activity-dependent regulation of astrocyte GAT levels during synaptogenesis

Allie K. Muthukumar, Wilm Tobias Stork, Marc Freeman

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Astrocytic uptake of GABA through GABA transporters (GATs) is an important mechanism regulating excitatory/inhibitory balance in the nervous system; however, mechanisms by which astrocytes regulate GAT levels are undefined. We found that at mid-pupal stages the Drosophila melanogaster CNS neuropil was devoid of astrocyte membranes and synapses. Astrocyte membranes subsequently infiltrated the neuropil coordinately with synaptogenesis, and astrocyte ablation reduced synapse numbers by half, indicating that Drosophila astrocytes are pro-synaptogenic. Shortly after synapses formed in earnest, GAT was upregulated in astrocytes. Ablation or silencing of GABAergic neurons or disruption of metabotropic GABA receptor 1 and 2 (GABA B R1/2) signaling in astrocytes led to a decrease in astrocytic GAT. Notably, developmental depletion of astrocytic GABA B R1/2 signaling suppressed mechanosensory-induced seizure activity in mutants with hyperexcitable neurons. These data reveal that astrocytes actively modulate GAT expression via metabotropic GABA receptor signaling and highlight the importance of precise regulation of astrocytic GAT in modulation of seizure activity.

Original languageEnglish (US)
Pages (from-to)1340-1350
Number of pages11
JournalNature Neuroscience
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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GABA Plasma Membrane Transport Proteins
Astrocytes
Synapses
GABA Receptors
Neuropil
Seizures
GABAergic Neurons
Membranes
Drosophila melanogaster
gamma-Aminobutyric Acid
Nervous System
Drosophila
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Activity-dependent regulation of astrocyte GAT levels during synaptogenesis. / Muthukumar, Allie K.; Stork, Wilm Tobias; Freeman, Marc.

In: Nature Neuroscience, Vol. 17, No. 10, 01.10.2014, p. 1340-1350.

Research output: Contribution to journalArticle

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